CN115778919A - Selenium-based antioxidant defense nano system for fluorescence-photoacoustic monitoring and spinal cord injury alleviation and application thereof - Google Patents
Selenium-based antioxidant defense nano system for fluorescence-photoacoustic monitoring and spinal cord injury alleviation and application thereof Download PDFInfo
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Abstract
The invention discloses a selenium-based antioxidant defense nano system for fluorescence-photoacoustic monitoring and spinal cord injury alleviation and application thereof, which is a composite nano material formed by connecting DSPE-PEG coated nano Se particles and BDP-DOH, and is named as Se @ BDP-DOHNPs. The invention has the advantages that the composite nano material combining Se and BDP-DOH with biocompatibility is constructed, the material is a nano system integrating the functions of oxidative stress photoacoustic monitoring and antioxidant repair, and can be applied to monitoring and treatment of oxidative stress after cell injury/spinal cord injury. The method can dynamically monitor the oxidative stress state after cell injury/spinal cord injury in real time, and has the effect of resisting oxidative stress. Provides a new idea for the research of relieving the oxidative stress after the spinal cord injury and provides a new method for the repair and treatment of the spinal cord injury.
Description
Technical Field
The invention relates to the technical field of monitoring and relieving spinal cord injury, in particular to selenium-based antioxidant defense nanotechnology.
Background
Spinal Cord Injury (SCI) is a condition in which external forces act directly and/or indirectly on the Spinal cord, resulting in structural and/or functional changes that lead to changes in sensation, movement, and sphincter dysfunction below the level of injury, dystonia, and pathological reflexes [1-3] . The pathophysiological processes of SCI are generally divided into primary and secondary injury [4] . Oxidative Stress (OS) is one of the major mechanisms of secondary injury to SCI [5] . OS is a state of imbalance between oxidation and antioxidation in vivo, and is prone to oxidation, resulting in inflammatory infiltration of neutrophils, increased secretion of protease, and generation of a large amount of oxidationIntermediate product [6] . Among them, reactive Oxygen Species (ROS) is widely considered as a main oxidizing agent [7-10] Such as superoxide anion (O) 2 ·- ) Hydrogen peroxide (H) 2 O 2 ) And hydroxyl radicals (& OH), leading to the diffusion and worsening of tissue damage, ultimately leading to motor dysfunction below the pathological level. Therefore, monitoring and eliminating oxidative stress is an effective approach for SCI therapeutic intervention.
Selenium (Se) is an indispensable trace element for human growth and development, is a semi-solid metal and is considered as a key factor of micronutrients participating in a plurality of biological processes [11] . It has important functions on the body, such as physiological functions of resisting oxidation, enhancing immunity, resisting inflammation, inhibiting tumor generation and the like. However, the safety margin for selenium intake is narrow. Biofunctional nanoparticles have been widely recognized as successful therapeutic agents and drug delivery systems with the advantages of small size, high surface area, surface charge, surface chemistry, solubility and sustained drug release. Currently, several nano-selenium particles (Se NPs) have been used as drug delivery vehicles with low toxicity and high biocompatibility [12] And can be used for resisting inflammation and resisting oxidative stress. However, the treatment process of spinal cord injury cannot be monitored in real time, so that the treatment process cannot be scientifically adjusted to promote repair of spinal cord injury to the maximum extent.
Currently, various fluorescent probes have made significant progress in studying the process of SCI secondary injury by monitoring oxidative stress [13,14] . Although these fluorescent sensors exhibit greater selectivity and sensitivity in monitoring oxidative stress, poor tissue permeability and limited water solubility pose difficulties in characterizing and exploring local SCI. In addition, some conventional imaging techniques [15-17] Such as Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET), are used for diagnosis and prognosis of spinal cord injuries with satisfactory time-space resolution. In addition, these methods have advantages in displaying SCI sites and monitoring blood flow, which can help clinicians assess therapeutic efficacy. However, these imaging techniques cannotThe progress of SCI is continuously reflected, and the technology often needs professional technology and is high in cost, so that the popularization and the development of the technology are limited. Therefore, a perfect spinal cord injury repair diagnosis and treatment probe has the functions of eliminating and responding to and monitoring the intracellular oxidative stress level state in real time.
Photoacoustic Imaging (PAI) is a rapidly developing non-invasive technique in bioimaging with strong contrast between the imaged tissue and the injected PA Imaging contrast agent [10] . When the pulse laser irradiates the biological tissue, the light absorption domain of the tissue generates an ultrasonic signal, the photoacoustic signal generated by the biological tissue carries the light absorption characteristic information of the tissue, and a light absorption distribution image in the tissue can be reconstructed by detecting the photoacoustic signal. There are a number of PA probes currently used to monitor metal ions or ROS. Wherein BDP-DOH is a monomolecular reversible PA probe based on near infrared boron dipyrromethene (BODIPY) dye, and O is dynamically and continuously monitored 2 ·- The redox cycling of GSH allows monitoring of local redox status in vivo. When BDP-DOH and O 2 ·- In combination, BDP-DOH is oxidized, the main absorption peak is red-shifted from 680nm to 750nm, and the photoacoustic signal generated by the corresponding exciting light is also shifted; when the latter is reduced by GSH, the absorption of the latter is restored and blue-shifted to 680nm, and the photoacoustic signal is restored to the initial state, thereby realizing reversible dynamic monitoring of the redox state [18] 。
[1]Witiw C D,Fehlings M G.Acute Spinal Cord Injury[J].J Spinal Disord Tech,2015,28(6):202-210.
[2]Ahuja C S,Wilson J R,Nori S,et al.Traumatic spinal cord injury[J].Nat Rev Dis Primers,2017,3:17018.
[3]Alizadeh A,Dyck S M,Karimi-Abdolrezaee S.Traumatic Spinal Cord Injury:An Overview of Pathophysiology,Models and Acute Injury Mechanisms[J].FrontNeurol,2019,10:282-282.
[4]Choo A M,Liu J,Liu Z,et al.Modeling spinal cord contusion,dislocation,and distraction:characterization of vertebral clamps,injury severities,and node of Ranvier deformations[J].J Neurosci Methods,2009,181(1):6-17.
[5]Von Leden R E,YaugerY J,Khayrullina G,et al.Central Nervous System Injury and Nicotinamide Adenine Dinucleotide Phosphate Oxidase:Oxidative Stress and Therapeutic Targets[J].J Neurotrauma,2017,34(4):755-764.
[6]Sies H,Berndt C,Jones D P.Oxidative Stress[J].Annu Rev Biochem,2017,86:715-748.
[7]Xiao H,Zhang W,Li P,et al.Versatile Fluorescent Probes for Imaging the Superoxide Anion in Living Cells and In Vivo[J].Angewandte Chemie International Edition,2020,59(11):4216-4230.
[8]Wu L,SedgwickA C,Sun X,et al.Reaction-Based Fluorescent Probes for the Detection and Imaging of Reactive Oxygen,Nitrogen,and Sulfur Species[J].Acc Chem Res,2019,52(9):2582-2597.
[9]Radi R.Oxygen radicals,nitric oxide,and peroxynitrite:Redox pathways in molecular medicine[J].Proc NatlAcad Sci U S A,2018,115(23):5839-5848.
[10]Gardner S H,Brady C J,Keeton C,et al.A General Approach to Convert Hemicyanine Dyes into Highly Optimized Photoacoustic Scaffolds for Analyte Sensing[J].Angew Chem Int Ed Engl,2021.
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J,et al.Selenium Anticancer Properties and Impact on Cellular Redox Status[J].Antioxidants(Basel),2020,9(1).
[12]Ferro C,Florindo H F,Santos H A.Selenium Nanoparticles for Biomedical Applications:From Development and Characterization to Therapeutics[J].Adv Healthc Mater,2021:e2100598.
[13]Kolanowski J L,Liu F,New E J.Fluorescent probes for the simultaneous detection of multiple analytes in biology[J].Chem Soc Rev,2018,47(1):195-208.
[14]Jiang Y,Fu P,Liu Y,et al.Near-infrared light-triggered NO release for spinal cord injury repair[J].SciAdv,2020,6(39).
[15]Zhang L,López-Picón F R,Jia Y,et al.Longitudinal[18F]FDG and[13N]NH3 PET/CT imaging of brain and spinal cord in a canine hemisection spinal cord injury model[J].NeuroImage:Clinical,2021,31:102692.
[16]Kumar Y,Hayashi D.Role of magnetic resonance imaging in acute spinal trauma:a pictorial review[J].BMC Musculoskeletal Disorders,2016,17(1):310.
[17]Kim J H,Song S K.Diffusion tensor imaging of the mouse brainstem and cervical spinal cord[J].Nat Protoc,2013,8(2):409-417.
[18]Zheng J,Zeng Q,Zhang R,et al.Dynamic-Reversible Photoacoustic Probe for Continuous Ratiometric Sensing and Imaging of Redox Status inVivo[J].J Am Chem Soc,2019,141(49):19226-19230.
Disclosure of Invention
The invention aims to provide a selenium-based antioxidant defense nano system for fluorescence-photoacoustic monitoring and spinal cord injury alleviation and application thereof, and aims to solve the problems that the redox state of intracellular/spinal cord injury cannot be monitored in a real-time response manner and the cell/spinal cord injury cannot be alleviated in the prior art.
In order to achieve the purpose, the invention adopts the following technical scheme:
the selenium-based antioxidant defense nano system is a composite nano material formed by connecting DSPE-PEG coated nano Se particles and BDP-DOH, and is named as Se @ BDP-DOH NPs.
A preparation method of the selenium-based antioxidant defense nano system comprises the following steps: taking Na 2 SeO 3 Adding DSPE-PEG into the solution, stirring to dissolve, adding vitamin C solution, mixing, stirring, filteringRemoving residual Na 2 SeO 3 Or DSPE-PEG, synthesizing DSPE-PEG coated nano Se particles, which are named Se NPs;
taking the Se NPs solution, then adding the BDP-DOH solution into the Se NPs solution, stirring, dialyzing and drying to obtain the composite nano material Se @ BDP-DOHNPs.
Further, the detailed steps include: preparing 40-100mM vitamin C solution and 10-100mM Na 2 SeO 3 A solution; take 2mLNa 2 SeO 3 Adding 40mg of DSPE-PEG into the solution, continuously stirring to completely dissolve the DSPE-PEG, and adding 2mL of vitamin C solution under stirring to thoroughly and uniformly mix the vitamin C solution; adding 6mL of distilled water into the mixed solution obtained in the step, maintaining the pH at 6.8-7.4, and continuously magnetically stirring at normal temperature; the mixture was then dialyzed and the residual Na was filtered off 2 SeO 3 Or DSPE-PEG, synthesizing Se NPs;
taking 1mL of 10mg/mL Se NPs aqueous solution, then adding 100 mu L of 1-3mg/100 mu L of BDP-DOH dimethyl sulfoxide solution, and stirring;
dialyzing with dialysis bag with cut-off molecular weight of 1000KDa, and drying to obtain composite nanometer material Se @ BDP-DOHNPs.
Further, the detailed steps include: preparing 40-100mM vitamin C solution and 10-100mM Na 2 SeO 3 A solution; take 2mLNa 2 SeO 3 Adding 40mg of DSPE-PEG into the solution, continuously stirring to completely dissolve the DSPE-PEG, and adding 2mL of vitamin C solution under stirring to thoroughly and uniformly mix the vitamin C solution; adding 6mL of distilled water into the mixed solution obtained in the step, adjusting the pH value by using 0.1M NaOH or 0.1M HCl to maintain the pH value at 7.1, and continuously magnetically stirring for 24 hours at normal temperature; the mixture was dialyzed for 24h and the residual Na was filtered off 2 SeO 3 Or DSPE-PEG, synthesizing Se NPs;
1mL of 10mg/mL Se NPs aqueous solution is taken, then 100 muL of 1mg/100 muL BDP-DOH dimethyl sulfoxide solution is added into the aqueous solution, and the mixture is stirred vigorously overnight;
dialyzing with dialysis bag with molecular weight cutoff of 1000KDa, and drying to obtain composite nanometer materials Se @ BDP-DOHNPs.
The invention also provides application of the selenium-based antioxidant defense nano system in researching a spinal cord injury mechanism and/or antioxidant repair of spinal cord injury.
The invention also provides application of the selenium-based antioxidant defense nano system in preparation of a medicine for monitoring spinal cord injury and/or antioxidant repair of spinal cord injury.
The invention also provides application of the selenium-based antioxidant defense nano system in researching an intracellular damage mechanism and/or antioxidant repair of cell damage.
The invention also provides application of the selenium-based antioxidant defense nano system in preparation of a medicine for monitoring cell damage and/or antioxidant repair of cell damage.
The advantages and effects of the invention include: the composite nano material combining Se and BDP-DOH with biocompatibility is constructed, is a nano system integrating the functions of oxidative stress photoacoustic monitoring and antioxidant repair, and can be applied to monitoring and treatment of oxidative stress after cell injury/spinal cord injury. Researches show that the compound can dynamically monitor the oxidative stress state after cell injury/spinal cord injury in real time and has the function of resisting oxidative stress. Therefore, the nano material is developed as a photoacoustic probe to monitor oxidative stress and resist oxidation, a new thought is provided for the research of relieving the oxidative stress after spinal cord injury, and a new method is provided for the repair and treatment of the spinal cord injury.
Drawings
FIG. 1A is a schematic diagram of a synthetic procedure according to an embodiment;
FIG. 1B is a particle size distribution histogram of example Di Se @ BDP-DOH NPs;
FIG. 1C is a diagram of an experimental observation of TAM of the example of di Se @ BDP-DOH NPs;
FIG. 2 is the example two addition of superoxide anion (O) 2 ·- ) Determining the absorption spectrum statistical chart of Se @ BDP-DOH NPs;
FIG. 3 is example two addition of O 2 ·- Determining the fluorescence spectrum statistical chart of BDP-DOH according to the existence of GSH;
FIG. 4 is a schematic view ofEXAMPLE two photoacoustic imager monitor O 2 ·- Experimental graphs of the influence of the existence of the Se @ BDP-DOH NPs on photoacoustic signals;
FIG. 5A is a statistical plot of a BDP-DOH cytotoxicity assay experiment;
FIG. 5B is a statistical plot of the Se NPs cytotoxicity assay;
FIG. 6 is an experimental and statistical plot of 400nM BDP-DOH cultured hippocampal neurons injured by glutamate of different concentrations;
FIG. 7 is a typical picture of different concentrations of Se NPs repairing damaged neurons;
FIG. 8 is a statistical plot of total neurite length versus number of injured neurons repaired by Se NPs at various concentrations;
FIG. 9 is a statistical plot of toxicity detection of Se @ BDP-DOH NPs on hippocampal neurons;
FIG. 10 is a graph showing the experimental effect of a fluorescent probe for Se @ BDP-DOH NPs;
FIG. 11 is a graph of an experiment of culturing injured hippocampal neurons at different concentrations of Se @ BDP-DOH NPs;
FIG. 12 is a statistical plot of hippocampal neurite outgrowth versus total length for different concentrations of Se @ BDP-DOH NPs culture lesions;
FIG. 13 is an experimental image of a photoacoustic imager after local injection of PBS, BDP-DOH and Se @ BDP-DOHNPs in the SD rat model with spinal cord injury;
FIG. 14 is a statistical plot of fluorescence intensity of each experimental group in spinal cord injury experiments;
FIG. 15 is a laser confocal microscope observation experiment chart of spinal cord tissue slices of each experiment group;
FIG. 16 is a statistical plot of fluorescence intensity of spinal cord tissue sections for each experimental group.
Detailed Description
The invention will be described in detail with reference to the drawings and specific embodiments, which are provided herein for the purpose of illustrating the invention and are not to be construed as limiting the invention.
Example preparation of Se @ BDP-DOH NPs
(1) The synthesis process of nano selenium particles (Se NPs) comprises the following steps: first, 100mM vitamin C solution and 100mM Na solution were prepared 2 SeO 3 And (3) solution. Get2mLNa 2 SeO 3 To the solution, 40mg of DSPE-PEG was added and stirring was continued to dissolve completely. Secondly, 2mL of vitamin C solution was added under stirring to thoroughly mix the solution. 6mL of distilled water was added to the mixture obtained in the above step, and the pH was adjusted to 7.1 using 0.1M NaOH or 0.1M HCl, and magnetic stirring was continued at room temperature for 24 hours. The mixture was then dialyzed for 24h and the residual Na was filtered off 2 SeO 3 Or DSPE-PEG, finally synthesizing nano Se particles (hereinafter referred to as Se NPs) coated with DSPE-PEG;
(2) The synthesis process of Se @ BDP-DOH NPs comprises the following steps:
1) Taking an aqueous solution of the nano Se particle Se NPs (10 mg/mL,1 mL) coated by the DSPE-PEG, adding a dimethyl sulfoxide solution (100 mu L) of BDP-DOH (1 mg) into the aqueous solution, and vigorously stirring the mixture overnight;
2) Then dialyzing by a dialysis bag with the molecular weight cutoff of 1000KDa, and drying to obtain the composite nano material Se @ BDP-DOH NPs.
The above preparation process can be seen in FIG. 1A.
Example characterization of Di Se @ BDP-DOH NPs
Particle size and morphology analysis: dripping a little Se @ BDP-DOH NPs solution into a sample pool of a dynamic light scattering analyzer DLS, analyzing the diameter of the Se @ BDP-DOH NPs, and measuring the particle size distribution of the Se @ BDP-DOH NPs, wherein the hydrated particle size of the Se @ BDP-DOH NPs is about 51.74nm as shown in figure 1B; meanwhile, the solution of Se @ BDP-DOH NPs is dropped on a copper net special for an electron microscope TEM, the solution is naturally dried at normal temperature, the shape of the particles is observed by the TEM, the appearance of the Se @ BDP-DOH NPs is characterized, the size of the diameter of the particles is measured, and the result is shown in figure 1C, wherein the particles are uniform and spherical particles with good dispersibility and the particle size is about 45nm.
Absorption spectrum and fluorescence spectrum of particles: in order to measure the optical properties of the particles, the addition of superoxide anion (O) was measured by a microplate reader 2 ·- ) Determining whether the change of the absorption spectrum and the fluorescence spectrum of the particle is detected; as a result, FIG. 2 shows that Se @ BDP-DOH NPs have the optical characteristics of BDP-DOH, i.e., O 2 ·- When present, the absorbance of the solution is from 680nm to750nm conversion. BDP-DOH can monitor O by reversible fluorescence conversion 2 ·- Dynamic case of GSH, as shown in FIG. 3.
Particle photoacoustic imaging: monitoring O by photoacoustic imager 2 ·- Presence or absence, change of photoacoustic signal thereof. As a result, as shown in FIG. 4, photoacoustics of Se @ BDP-DOH NPs showed that the absorbance was converted from 680nm to 750nm in the presence of superoxide anion.
Example TriBDP-DOH fluorescent Probe Effect in cells and antioxidant Effect of Se NPs
Cytotoxicity: cell Counting Kit-8 (CCK-8) was used to test the cytotoxicity of BDP-DOH and Se NPs. Culturing hippocampal neurons with BDP-DOH of different concentrations (25. Mu.M, 50. Mu.M, 100. Mu.M, 200. Mu.M, 400. Mu.M, 800. Mu.M), observing fluorescence change with a confocal microscope, selecting a proper concentration, as shown in FIG. 5A, BDP-DOH has little toxicity to hippocampal neurons, and selecting a concentration of 400nM in subsequent experiments; the hippocampal neurons were cultured with Se NPs at different concentrations (1.56. Mu.M, 3.13. Mu.M, 6.25. Mu.M, 12.5. Mu.M, 25. Mu.M, 50. Mu.M, 100. Mu.M, 150. Mu.M, 200. Mu.M) and fluorescence changes were observed by confocal microscopy, as shown in FIG. 5B, where the concentration of Se NPs was greater than 50. Mu.M, cytotoxicity was more pronounced.
Fluorescence behavior of BDP-DOH and antioxidant action of Se NPs: the higher the glutamic acid concentration, the more severe the damage of hippocampal neurons, and after the damage of hippocampal neurons with glutamic acid of various concentrations (60. Mu.M, 120. Mu.M, 180. Mu.M, 240. Mu.M, 300. Mu.M, 360. Mu.M), the change in fluorescence was observed with a confocal microscope by culturing with 400nM BDP-DOH, as shown in FIG. 6, and the fluorescence intensity of BDP-DOH at 647nM decreased with the increase in the severity of damage of hippocampal neurons, thus demonstrating that the severity of cell damage can be observed with the fluorescence intensity of BDP-DOH. In the data statistical chart of fig. 6, the ordinate is intensity, the coordinate values are 20, 30, 40, 50, 60, and 70 in order from bottom to top, the abscissa is Glu (μ M), and the coordinates are control, 60, 120, 180, 240, 300, and 360 in order from left to right.
Injured hippocampal neurons were cultured with different concentrations (6.25. Mu.M, 1.56. Mu.M, 3.125. Mu.M, 12.5. Mu.M, 25. Mu.M, 50. Mu.M) of Se NPs, and fluorescence changes were observed by confocal microscopy, as shown in FIG. 7 (Se stands for Se NPs) which is a typical picture of injured neurons repaired by different concentrations of Se NPs. The total length and number of the protrusions were counted, and the results are shown in FIG. 8 (Se stands for Se NPs) where the concentration of Se NPs was 6.25. Mu.M.
Example fluorescent Probe Effect of TetraSe @ BDP-DOH NPs in cells and antioxidant Effect thereof
Cytotoxicity: cell Counting Kit-8 (CCK-8) was used to test the toxicity of Se @ BDP-DOH NPs on hippocampal neurons. As shown in FIG. 9 (in the figure, se @ BDP-DOH stands for Se @ BDP-DOH NPs), and the concentration range of Se @ BDP-DOH NPs is 0-50 μ M with low toxicity.
Fluorescent probe action of Se @ BDP-DOH NPs: labeling hippocampal neuron microtubules with an antibody Tubulin, observing the co-localization of microtubules and Se @ BDP-DOH NPs through a laser confocal microscope, wherein Se @ BDP-DOH represents Se @ BDP-DOH NPs in the figure and can be used as a probe as shown in figure 10.
Antioxidant action of Se @ BDP-DOH NPs: injured hippocampal neurons were cultured with Se @ BDP-DOH NPs at various concentrations (1.56. Mu.M, 3.125. Mu.M, 6.25. Mu.M, 12.5. Mu.M, 25. Mu.M, 50. Mu.M) and their numbers of processes and total length were counted. As shown in FIGS. 11-12 (Se @ BDP-DOH stands for Se @ BDP-DOH NPs), se @ BDP-DOH NPs with different concentrations can repair damaged hippocampal neurons in different degrees.
Example photoacoustic Probe Effect of pentaSe @ BDP-DOH NPs in vivo and antioxidant Effect thereof
Photoacoustic imaging of Se @ BDP-DOH NPs: constructing a spinal cord injury SD rat model, locally injecting PBS, BDP-DOH and Se @ BDP-DOH NPs for 3 days continuously according to different groups after the model is established, and then imaging by using a photoacoustic imager. FIG. 13 shows that (Se @ BDP-DOH stands for Se @ BDP-DOH NPs) BDP-DOH can be used as a photoacoustic probe to monitor the oxidative stress state in vivo, and Se-bearing Se @ BDP-DOH NPs can reduce oxidative stress after spinal cord injury. As shown in FIG. 14 (M represents Mild injury, H represents Heavy injury, se @ BDP-DOH represents Se @ BDP-DOH NPs), in spinal cord injury, compared with BDP-DOH group, the fluorescence intensity of Se @ BDP-DOH NPs group at 680nm is obviously enhanced, which indicates that the oxidative stress of Se @ BDP-DOHNPs group is obviously reduced.
In addition, spinal cord tissue sections were taken from each group after 4% paraformaldehyde infusion. Fluorescence of the laser confocal microscope at 647nm is observed, as shown in FIGS. 15-16 (Se stands for Se @ BDP-DOH NPs), and the fluorescence intensity of the tissue section also shows that Se @ BDP-DOH NPs can obviously reduce the oxidative stress level.
The technical solutions provided by the embodiments of the present invention are described in detail above, and specific examples are applied herein to explain the principles and embodiments of the present invention, and the descriptions of the embodiments above are only used to help understanding the principles of the embodiments of the present invention; meanwhile, for a person skilled in the art, according to the embodiments of the present invention, there may be variations in the specific implementation manners and application ranges, and in summary, the content of the present description should not be construed as a limitation to the present invention.
Claims (8)
1. Selenium-based antioxidant defense nanosystems, characterized in that:
the composite nano material is formed by connecting DSPE-PEG coated nano particles and BDP-DOH and is named Se @ BDP-DOHNPs.
2. A method of preparing a selenium-based antioxidant defense nanosystem as claimed in claim 1, characterized in that:
the method comprises the following steps: taking Na 2 SeO 3 Adding DSPE-PEG into the solution, stirring to dissolve, adding vitamin C solution, mixing, stirring, and filtering to remove residual Na 2 SeO 3 Or DSPE-PEG, synthesizing nano Se particles coated by the DSPE-PEG, which are named as Se NPs;
taking the Se NPs solution, then adding the BDP-DOH solution into the Se NPs solution, stirring, dialyzing and drying to obtain the composite nano material Se @ BDP-DOHNPs.
3. The method of claim 2, wherein the selenium-based antioxidant defense nanosystems are prepared by:
the detailed steps comprise: preparing 40-100mM vitamin C solution and 10-100mM Na 2 SeO 3 A solution; 2mL of Na was taken 2 SeO 3 Adding 40mg of DSPE-PEG into the solution, continuously stirring to completely dissolve the DSPE-PEG, and adding 2mL of vitamin C solution under stirring to thoroughly and uniformly mix the solution; adding 6mL of distilled water into the mixed solution obtained in the step, maintaining the pH at 6.8-7.4, and continuously magnetically stirring at normal temperature; the mixture was then dialyzed and the residual Na was filtered off 2 SeO 3 Or DSPE-PEG, synthesizing Se NPs;
taking 1mL of 10mg/mL Se NPs aqueous solution, then adding 100 mu L of 1-3mg/100 mu LBDP-DOH dimethyl sulfoxide solution, and stirring;
dialyzing with dialysis bag with cut-off molecular weight of 1000KDa, and drying to obtain composite nanometer material Se @ BDP-DOHNPs.
4. The method of claim 2, wherein the selenium-based antioxidant defense nanosystems are prepared by:
the detailed steps comprise: preparing 40-100mM vitamin C solution and 10-100mM Na 2 SeO 3 A solution; 2mL of Na was taken 2 SeO 3 Adding 40mg of DSPE-PEG into the solution, continuously stirring to completely dissolve the DSPE-PEG, and adding 2mL of vitamin C solution under stirring to thoroughly and uniformly mix the vitamin C solution; adding 6mL of distilled water into the mixed solution obtained in the step, adjusting the pH value by using 0.1M NaOH or 0.1M HCl to maintain the pH value at 7.1, and continuously magnetically stirring for 24 hours at normal temperature; the mixture was dialyzed for 24h and the residual Na was filtered off 2 SeO 3 Or DSPE-PEG, synthesizing Se NPs;
1mL of 10mg/mL Se NPs aqueous solution is taken, then 100 muL of 1mg/100 muL BDP-DOH dimethyl sulfoxide solution is added into the aqueous solution, and the mixture is stirred vigorously overnight;
dialyzing with dialysis bag with cut-off molecular weight of 1000KDa, and drying to obtain composite nanometer material Se @ BDP-DOHNPs.
5. Use of the selenium-based antioxidant defense nanosystems of claim 1 for studying the mechanisms of spinal cord injury and/or for antioxidant repair of spinal cord injury.
6. Use of a selenium-based antioxidant defense nanosystem as defined in claim 1 for the manufacture of a medicament for monitoring and/or antioxidant repair of spinal cord injury.
7. Use of the selenium-based antioxidant defense nanosystems of claim 1 for the study of intracellular damage mechanisms and/or antioxidant repair of cellular damage.
8. Use of a selenium-based antioxidant defense nanosystem as defined in claim 1 for the manufacture of a medicament for monitoring cell damage and/or antioxidant repair of cell damage.
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